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IFN induction by TLR3 and TLR4 stimulation A significant amount of work in our laboratory has been based on examining the biological outcomes of signaling in B cells via CD40, a cell surface protein that is a mem-ber of the TNF receptor superfamily. When activated by its cognate ligand, CD40 initiates a signaling cascade that results in activation of NF-κB, JNK, p38 and PI3K.1 This series of events, in turn, leads to functional out-comes that serve the adaptive immune response, such as enhanced survival and the formation of germinal centers. Interestingly, TLRs had been shown to utilize these sig-naling pathways to activate a set of innate immune func-tions. In order to understand the specificities between the TLR and TNFR families in the activation of B lympho-cytes, we conducted a Genechip microarray analysis of primary murine B cells stimulated with LPS and CD40L. We were interested to find that while LPS and CD40 stimulation induced a large set of overlapping genes, LPS stimulation specifically induced a subset of genes that had previously been classified as interferon-responsive. Furthermore, we found that the induction of these antiviral genes in primary macrophages and RAW cells occurred upon stimulation of TLR3 or TLR4 with the dsRNA ligand poly I:C and LPS, respectively. This suggested that while TLR signaling may use common downstream components such as NF-κB, TLR3/4 also activated a unique set of fac-tors to mediate the induction of a specific gene subset that required the interferon-responsive transcription factor IRF-3. Furthermore, stimulation of TLR4 or, to a greater extent, TLR3, directly led to production of IFN-β, a type I IFN family member, in stimulated macrophages.